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Journal of Virology, January 2007, p. 74-83, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01269-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Rapid Memory CD8+ T-Lymphocyte Induction through Priming with Recombinant Mycobacterium smegmatis{triangledown}

Avi-Hai Hovav,1 Mark J. Cayabyab,1 Michael W. Panas,1 Sampa Santra,1 John Greenland,1 Ralf Geiben,1 Barton F. Haynes,2 William R. Jacobs Jr.,3 and Norman L. Letvin1*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115,1 Duke University School of Medicine, Durham, North Carolina 27710,2 Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 104613

Received 15 June 2006/ Accepted 10 October 2006

The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4+ T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant-mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant-mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8+ T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.

* Corresponding author. Mailing address: Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115. Phone: (617) 667-2042. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

{triangledown} Published ahead of print on 18 October 2006.

Journal of Virology, January 2007, p. 74-83, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01269-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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